Folic Acid Supplements Won't Lower Heart-Attack Risk

Three B vitamins, folic acid, B12 and B6 are known to be necessary to properly metabolize the amino acid, methionine.  Homocysteine, an intermediate product of methionine metabolism, causes oxidation damage to tissues and is believed to contribute to atherosclerosis, heart disease and strokes.  Deficiencies of folic acid, B12 and B6 can allow homocysteine to build up and increase the chance of cardio vascular disease and possibly other conditions of ill health.

Two recent studies have reported no decrease in risk for cardiovascular events in subjects taking a combination of these three vitamins (see http://content.nejm.org/cgi/reprint/NEJMoa060900.pdf and http://content.nejm.org/cgi/reprint/NEJMoa055227.pdf for original reports).

As commented below, "These studies did not test whether B vitamins used by healthy people can help keep them healthy,  Instead, they looked at whether B vitamins can treat or reverse heart disease in people who already have it."  This is a good point.  Once the heart is damaged, we cannot assume that taking certain nutrients will repair the injury and restore the heart to normal health.  Similarly, you can't repair tire damage caused by a tire being under-inflated by restoring proper inflation; the life time of the tire will still be decreased.  However, restoring proper tire pressure may decrease the rate of wear and tear to normal.

Alice H. Lichtenstein, director of the Cardiovascular Nutrition Lab at the USDA Human Nutrition Research Center at Tufts University is quoted as saying, "This is one of those cases where you see an association with reduced risk of heart disease with levels of vitamins that would normally be consumed, but when you go to considerably higher levels than people could consume from diet, we get disappointing results,"  The fact is, subjects in both studies were given only folic acid, B12 and B6, whereas B vitamins are normally consumed as the entire B-complex.  It may not be the "higher levels" of vitamins that is relevant, but the fact that the rest of the B-complex was not included. This would increase the chance of nutritional imbalance negatively impacting health.  There is no mention of whether the subjects supplemented with other B vitamins, or whether they might be deficient in certain vitamins B1 which can cause beriberi symptoms including heart failure (see http://www.nlm.nih.gov/medlineplus/ency/article/000339.htm).   If subjects took a B-complex vitamin which included adequate amounts of folic acid, B12 and B6, general health might have been better promoted in these studies and results might have been more positive.

John W. Cartmell, MS
www.dietadvisor.com


Folic Acid Supplements Won't Lower Heart-Attack Risk
3-12-06
 http://www.forbes.com/lifestyle/health/feeds/hscout/2006/03/12/hscout531507.html

SUNDAY, March 12 (HealthDay News) -- Two new studies question the conventional wisdom that folic acid and B vitamin supplementation lowers cardiovascular risk.

The logic behind supplementation has been that it reduces blood levels of a protein called homocysteine, long linked to heart attack and stroke. But the new research suggests that lowering homocysteine this way has no effect on preventing heart attacks -- and may even trigger a slight rise in heart attack risk.

Both reports will appear in the March 16 issue of the New England Journal of Medicine, but were released early to coincide with their presentation Sunday at the meeting of the American College of Cardiology, in Atlanta.

"Combination vitamin therapies, which do lower homocysteine, have no effect on cardiovascular events, even though the homocysteine level is lowered," said Dr. Joseph Loscalzo, head of the department of medicine at Brigham & Women's Hospital in Boston, and author of an accompanying journal editorial.

There was one glimmer of hope for people taking these supplements, however: One of the two studies did note a "marginally significant" decrease in stroke risk after supplementation.

In the first study, called the Norwegian Vitamin (NORVIT) trial, Norwegian researchers randomly assigned 3,749 men and women who had heart attacks to receive folic acid, vitamins B6 and B12, or a placebo.

Over the three years of the trial, the researchers found that while homocysteine levels dropped an average of 27 percent among people taking folic acid and vitamin B12, this decline in the blood protein had no significant effect on whether people had another heart attack or died from another heart attack.

In fact, people taking all three supplements actually experienced a slightly increased risk of having another heart attack, the researchers found.

"The NORVIT trial demonstrated that intervention with folic acid, with or without high doses of vitamin B6, did not lower the risk of recurrent cardiovascular disease or death after an acute myocardial infarction [heart attack]," the researchers wrote. "Such therapy may even be harmful after acute myocardial infarction or coronary stenting and should therefore not be recommended," they concluded.

In the second study, called the Heart Outcomes Prevention Evaluation (HOPE) 2 study, researchers gave more than 5,500 patients who had diabetes or vascular disease folic acid, vitamins B12 and B6, or a placebo.

Over the five years of the study, homocysteine levels dropped significantly among those receiving the supplements, but -- just as happened with the NORVIT trial -- this lowering of homocysteine did not result in significantly reduced risk of death from heart disease or heart attacks.

There did, however, appear to be a slight reduction in stroke among people taking the supplements, the researchers reported.

Overall, however, the researchers concluded that "combined daily administration of 2.5 mg [milligrams] of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12 for five years had no beneficial effects on major vascular events in a high-risk population with vascular disease."

They added that "our results do not support the use of folic acid and B vitamin supplements as a preventive treatment."

However, Anne Dickinson, a consultant and past president of the Council for Responsible Nutrition, which represents the supplements industry, said the findings may not apply to relatively healthy Americans who are turning to these vitamins to help ward off heart disease.

She noted that the two study populations involved sicker individuals with a history of heart attack, heart disease, diabetes and other problems.

"These studies did not test whether B vitamins used by healthy people can help keep them healthy," Dickinson said in a prepared statement. "Instead, they looked at whether B vitamins can treat or reverse heart disease in people who already have it. Vitamins should not be expected to perform like drugs -- their greatest purpose is in prevention."

But Alice H. Lichtenstein, director of the Cardiovascular Nutrition Lab at the USDA Human Nutrition Research Center at Tufts University, in Boston, countered that argument. She noted that even outwardly "healthy" Americans develop some level of atherosclerosis -- hardening of the arteries -- as they age, and so the findings would probably apply to the average consumer, as well.

Loscalzo thinks that the message from these studies may not be that lowering homocysteine doesn't prevent heart attacks, but rather that vitamin therapy is not the best way to lower homocysteine.

"These trials of vitamin therapy for high homocysteine have all been consistent in their message, namely, [that] combination vitamin therapies, which do lower homocysteine, have no effect on cardiovascular events, even though the homocysteine level is lowered," he said.

Loscalzo said he believes the supplement treatment somehow counteracts the effect of lowering homocysteine. "Some of those adverse affects may have to do with the complex metabolism of the vitamins," he said. "These vitamins are important for cell growth. It may be that the doses used might have stimulated the growth of cell and atherosclerotic plaque."

According to Loscalzo, there's strong evidence that homocysteine does adversely affect blood vessels. So perhaps the answer lies in smaller doses of vitamins.

"These high doses of folic acid don't provide any benefit and shouldn't be used," Loscalzo said. "Lower doses are safe and may provide benefit, but we don't know that yet.

"It's not that homocysteine is no longer a bad actor," Loscalzo said. "It's that lowering it with this simple treatment isn't the answer."

Lichtenstein agreed that high doses of vitamins may not be as beneficial as some have thought.

"This is one of those cases where you see an association with reduced risk of heart disease with levels of vitamins that would normally be consumed, but when you go to considerably higher levels than people could consume from diet, we get disappointing results," she said.


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